title: VSTM2L is a novel secreted antagonist of the neuroprotective peptide Humanin.
abstract: Humanin (HN) is a 24-residue peptide displaying a protective activity in vitro against a range of cytotoxic and neurotoxic insults, as well as mediating in vivo amelioration of Alzheimer disease (AD)-related memory impairment in experimental models. Published evidence suggests that the mechanisms through which HN exerts its cyto- and neuroprotective activity may include its secretion and binding to membrane-associated receptors. Here, we describe the identification of a new modulator of HN neuroprotective activity, V-set and transmembrane domain containing 2 like (VSTM2L), previously known as C20orf102. VSTM2L interacts with HN in both yeast and mammalian cells, is secreted in cultured cells, is present in serum, and is selectively expressed in the central nervous system. VSTM2L colocalizes with HN in distinct brain areas as well as in primary cultured neurons, where it plays a role in the modulation of neuronal viability. When tested in HN neuroprotection bioassays, VSTM2L acts as a strong antagonist of HN neuroprotective activity. In summary, VSTM2L is the first example of a secreted antagonist of HN and may play a role in the modulation of HN biological functions.
authors.affiliation: Siena Biotech SpA, Strada del Petriccio e Belriguardo n°35, 53100 Siena, Italy.
authors.forename: Lara
authors.initials: L
authors.lastname: Rossini
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Suzuki
authors.forename: Megumi
authors.initials: M
authors.lastname: Kurita
authors.forename: Marco
authors.initials: M
authors.lastname: Gianfriddo
authors.forename: Carla
authors.initials: C
authors.lastname: Scali
authors.forename: Renza
authors.initials: R
authors.lastname: Roncarati
authors.forename: Davide
authors.initials: D
authors.lastname: Franceschini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pollio
authors.forename: Lorenza
authors.initials: L
authors.lastname: Trabalzini
authors.forename: Georg C
authors.initials: GC
authors.lastname: Terstappen
authors.forename: Masaaki
authors.initials: M
authors.lastname: Matsuoka
authors.forename: Andrea
authors.initials: A
authors.lastname: Caricasole
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012441:Saccharomyces cerevisiae; D013116:Spinal Cord / Q000378:metabolism; D020798:Two-Hybrid System Techniques
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C560310:VSTM2L protein, human; C427211:humanin